The present invention is directed to the field of solubilization of hydrophobic materials. More particularly, the invention describes the use of certain lysophospholipids as solubilizers and non-toxic delivery vehicles.
The solubilization of hydrophobic materials, particularly bioactive materials, is typically achieved by the use of surfactants such as sodium deoxycholate or propylene glycol. Such surfactants, due to their detergent properties, are biologically incompatible and toxic due to their lytic effects on cells. It would, therefore, be desirable to employ a naturally occurring substance without toxic properties as a surfactant for pharmaceutical use.
Lysophospholipids have heretofore been improbable candidates for pharmaceutical excipients due to their lytic effects on cells. We describe a method and compositions for a lysophosphatide, specifically lysophosphatidylethanolamine, alone and in combination with an unsaturated phospholipid for solubilizing hydrophobic materials.
Peterson et al., Arch Biochem Biophys, 179, 218-228 (1977), observed lysophosphatidylethanolamine's (LPE) properties, as an ATPase inhibitor in biomembranes; these effects probably due to LPE intrusion into the membrane around the enzyme resulting in a less fluid lipid environment. Lysophospholipid suspensions were mixed with fractions of sacroplasmic spectrophotometric assay. LPE, however, unlike lysophosphatidylcholine, never solubilized biomembrane at any concentration.
The present invention exploits the pH and temperature dependent phase transitions of lysophosphatidylethanolamines to result in micellar solubilization of hydrophobic materials and delivery of a non-toxic product.